Treatment of cultured mammalian normal rat kidney (NRK) cells with picolinic acid, histidinol, or N-alkyl,N-nitrosoureas, or subjecting them to isoleucine deficiency results in a time dependent increase in the ability of prostaglandin E1 (PGE1), isoproterenol, or cholera toxin to increase intracellular cyclic adenosine 3',5' monophosphate (cAMP) levels. Similar increases in hormonal responses are observed in SV40 and Moloney sarcoma virus transformed NRK cells treated with picolinic acid. The increased response in NRK cells is due, at least in part, to a specific potentiation of GTP dependent events in hormonal activation of adenylate cyclase.